monoacylglyserolilipaasi

Monoacylglycerol lipase, abbreviated MAGL, is a serine hydrolase enzyme that catalyzes the hydrolysis of monoacylglycerols to glycerol and a free fatty acid. It is known by several names, including monoacylglycerol lipase and monoglyceride lipase, and in some languages it is referred to as monoacylglyserolilipaasi. In humans the enzyme is encoded by the MGLL gene. The catalytic mechanism employs a serine–histidine–aspartate triad characteristic of alpha/beta hydrolase enzymes, with active-site residues such as Ser122, His269 and Asp239 described in various species.

MAGL acts primarily on monoacylglycerols, with a preference for long-chain species such as 2-arachidonoylglycerol (2-AG), the principal endocannabinoid in many tissues. By hydrolyzing 2-AG, MAGL regulates endocannabinoid signaling and tone, influencing synaptic transmission and inflammatory responses. The enzyme also participates in general lipid turnover by hydrolyzing monoacylglycerols derived from dietary triglyceride digestion and endogenous lipid turnover.

Localization studies show MAGL in multiple cellular compartments, including the endoplasmic reticulum and the cytosol, and it can associate with lipid droplets in certain cell types. The enzyme is widely expressed, with relatively high levels in brain, liver and adipose tissue, reflecting its roles in both signaling and metabolism.

Regulation and inhibition of MAGL have been explored extensively. Selective MAGL inhibitors, such as JZL184 and related compounds, irreversibly inactivate the enzyme and raise tissue levels of 2-AG, producing analgesic and anti-inflammatory effects in animal models. Chronic MAGL inhibition can lead to compensatory changes and CB1 receptor desensitization.

The MGLL gene encodes MAGL in humans, and genetic or pharmacological disruption of MAGL underscores its importance in lipid signaling and metabolic regulation. Because of its central role in endocannabinoid signaling and lipid metabolism, MAGL is a target of interest for potential therapies in pain, neurodegenerative diseases and metabolic disorders.